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EMBO reports 7, 7, 727–733 (2006)
doi:10.1038/sj.embor.7400700
AOP Published online: 28 April 2006
c-Abl acetylation by histone acetyltransferases regulates its nuclear–cytoplasmic localization
Maria Giovanna di Bari1, 2, Laura Ciuffini3, Michele Mingardi1, 2, 4, Roberto Testi2, Silvia Soddu3 & Daniela Barilà1, 2, 4
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1 Dulbecco Telethon Institute, Via Montpellier 1, 00133 Rome, Italy
2 Laboratory of Immunology and Signal Transduction, Department of Experimental Medicine and Biochemical Sciences, University of Rome 'Tor Vergata', Via Montpellier 1, 00133 Rome, Italy
3 Department of Experimental Oncology, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy
4 Laboratory of Cell Signaling, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia, Via Fosso di Fiorano 64, 00143 Rome, Italy
To whom correspondence should be addressed
Daniela Barilà Tel: +39 06 50170 3168; Fax: +39 06 50170 3330; E-mail: daniela.barila@uniroma2.it; dbarila@dti.telethon.it
Received 8 August 2005; Accepted 5 April 2006; Published online 28 April 2006.
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Abstract
c-Abl function is strictly dependent on its subcellular localization. Using an in vitro approach, we identify c-Abl as a new substrate for p300, CBP (CREB-binding protein) and PCAF (p300/CBP-associated factor) histone acetyltransferases. Remarkably, acetylation markedly alters its subcellular localization. Point mutagenesis indicated that Lys 730, located in the second nuclear localization signal, is the main target of p300 activity. It has previously been reported that c-Abl accumulates in the cytoplasm during myogenic differentiation. Here, we show that c-Abl protein is acetylated at early stages of myogenic differentiation. Indeed, acetylation on Lys 730 drives c-Abl accumulation in the cytoplasm and promotes differentiation. Thus, Lys 730 acetylation is a novel post-translational modification of c-Abl and a novel mechanism for modulating its subcellular localization that contributes to myogenic differentiation.
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